What is the role of testing for genetic mutations in patients and/or family members following a venous thromboembolism?

Adults with a previous venous thromboembolism (VTE) and a factor V leiden (FVL) genetic mutation are at an increased risk of recurrent VTE compared with those without the mutation. Individuals with a prothrombin G20210A mutation are not at an increased risk of recurrent VTE compared with those without the mutation. There was no significant difference in the risk of recurrent VTE with anticoagulation therapy in patients with or without a genetic mutation. Family members of individuals with a previous VTE and the FVL mutation are at an increased risk of VTE, but there is no patient-oriented evidence that supports the testing or treating of family members. (LOE = 1a)

Segal JB, Brotman DJ, Necochea AJ, et al. Predictive value of factor V leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation. A systematic review. JAMA 2009;301(23):2472-2485.  [PMID:19531787]

Systematic review

Government

Various (meta-analysis)

Clinically relevant outcomes associated with testing for genetic risks for VTE are uncertain. These investigators searched multiple databases including MEDLINE, EMBASE, the Cochrane Library, and others for English-language-only studies evaluating outcomes associated with testing for FVL and prothrombin G20210A, the 2 most common inherited risk factors associated with VTE. The included studies assessed rates of VTE in individuals with a history of VTE or in family members of patients positive for these mutations. The authors also included studies that assessed harms and benefits associated with testing. Two individuals independently identified and critically assessed articles for eligibility and methodologic quality using standard criteria. A third individual adjudicated discrepancies in assessments. A total of 46 articles met the inclusion criteria; overall study quality was moderate. Recurrent VTE occurred significantly more often in patients with previous VTE (probands) who tested positive for the FVL mutation compared with probands without a genetic mutation. Family members of probands with the FVL mutation were also significantly more likely to experience a VTE than proband family members without the FVL mutation. Neither probands nor family members of probands with the prothrombin G20210A mutation had a statistically significant increased risk of recurrent VTE compared with similar individuals without the mutation. There was no evidence of significant heterogeneity or publication bias. Although anticoagulation reduced the risk of recurrent VTE in probands with a genetic mutation, there was no significant difference in the risk of recurrent VTE with anticoagulation therapy in probands with or without a genetic mutation. Evidence is insufficient to assess any value of testing for genetic mutations in family members of probands.